Perilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue

• Souza, Sandra C.

• Christoffolete, Marcelo A.

• Ribeiro, Miriam O.

• Miyoshi, Hideaki

• Strissel, Katherine J.

• Stancheva, Zlatina S.

• Rogers, Nicole H.

• D'Eon, Tara M.

• Perfield, James W., II

• Imachi, Hitomi

• Obin, Martin S.

• Bianco, Antonio C.

• Greenberg, Andrew S.

抄録

In response to cold, norepinephrine (NE)-induced triacylglycerol hydrolysis (lipolysis) in adipocytes of brown adipose tissue (BAT) provides fatty acid substrates to mitochondria for heat generation (adaptive thermogenesis). NE-induced lipolysis is mediated by protein kinase A (PKA)-dependent phosphorylation of perilipin, a lipid droplet-associated protein that is the major regulator of lipolysis. We investigated the role of perilipin PKA phosphorylation in BAT NE-stimulated thermogenesis using a novel mouse model in which a mutant form of perilipin, lacking all six PKA phosphorylation sites, is expressed in adipocytes of perilipin knockout (Peri KO) mice. Here, we show that despite a normal mitochondrial respiratory capacity, NE-induced lipolysis is abrogated in the interscapular brown adipose tissue (IBAT) of these mice. This lipolytic constraint is accompanied by a dramatic blunting (∼70%) of the in vivo thermal response to NE. Thus, in the presence of perilipin, PKA-mediated perilipin phosphorylation is essential for NE-dependent lipolysis and full adaptive thermogenesis in BAT. In IBAT of Peri KO mice, increased basal lipolysis attributable to the absence of perilipin is sufficient to support a rapid NE-stimulated temperature increase (∼3.0°C) comparable to that in wild-type mice. This observation suggests that one or more NE-dependent mechanism downstream of perilipin phosphorylation is required to initiate and/or sustain the IBAT thermal response.

収録刊行物

• Journal of lipid research

  Journal of lipid research 48 (6), 1273-1279, 2007-06

  American Society for Biochemistry and Molecular Biology

キーワード

• norepinephrine-induced thermal response
• protein kinase A-stimulated lipolysis
• brown adipocytes

詳細情報

• CRID: 1050845763954291072
• NII論文ID: 120006352221
• HANDLE: 2115/67272
• ISSN: 00222275
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles